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Biomedical subjects

U Keller

Publications and source records attributed to U Keller.

At least 199 records · Page 11Linked to original sources

[Swiss simvastatin multicenter study: 1. Efficacy of 10 mg simvastatin daily in patients with primary hypercholesterolemia].

In a Swiss multicenter study with determination of lipid and lipoprotein parameters in a central laboratory, the efficacy of simvastatin, MSD, was evaluated in patients with primary hypercholesterolemia. Lipid and lipoprotein values were determined in 109 patients before and after 6 weeks' therapy with 10 mg simvastatin per day. A significant decrease in total cholesterol, LDL-cholesterol and apo B, of 21.1, 25.8 and 24.1% respectively, was observed. No influence of simvastatin on apo A-II was found, but HDL-cholesterol and apo A-I were slightly increased (+6.1 and 4.4% respectively). The data show that HMG-CoA reductase inhibitors constitute a new class of effective drugs for the treatment of hypercholesterolemia.

Adult↗

Warning symptoms of hypoglycaemia during treatment with human and porcine insulin in diabetes mellitus.

32 subjects with long-term insulin-dependent diabetes mellitus (IDDM) were entered into a double-blind, randomised crossover trial with human and porcine insulin. They were treated during both periods with regular insulin and with protamine (NPH) insulin. 18 subjects started with human and 14 with porcine insulin; the two insulin periods each lasted twelve weeks; the insulin doses were much the same in the two periods (mean 23 [SD 9] U daily NPH; 14 [7] U daily regular insulin), as were blood glucose profiles and HbA1c values. There were 171 episodes of hypoglycaemia during human and 150 episodes during porcine insulin. Patients completed questionnaires after each hypoglycaemic episodes and at the end of the trial. Hunger and sweating without concomitant neuroglycopenic symptoms were significantly more frequent as initial warning symptoms during porcine than during human insulin (41% vs 20%), whereas neuroglycopenic symptoms were more frequent during human insulin. At the end of the trial 18 of 32 subjects reported diminished awareness of hypoglycaemia during human insulin compared with 6 of 32 during porcine insulin. Hypoglycaemia developed faster during human than during porcine insulin administration. The transfer of IDDM subjects from porcine to human insulin seems to alter warning symptoms of low blood glucose concentration, with consequent impairment of its early recognition.

Adult↗

[The sugar substitutes fructose and sorbite: an unnecessary risk in parenteral nutrition].

The glucose substitutes fructose, sorbitol and xylitol are still widely used in parenteral nutrition throughout central Europe. Their main advantage, which has led to their widespread use, is their diminished blood glucose raising effect and the absence of a browning reaction during sterilization with amino acids. During infusions with glucose substitutes in severely ill patients with glucose intolerance it is sometimes possible to avoid insulin therapy since the first steps in the metabolism of these carbohydrates are insulin-independent. These advantages are less relevant today since fat emulsions frequently replace some of the glucose given as energy substrate in parenteral nutrition and glucose intolerance is easier to monitor and to treat. - Specific advantages of xylitol are proposed, but this issue needs further clarification. The major objection to fructose, and therefore also to sorbitol, which is metabolized via fructose, is the life-threatening risk in patients with hereditary fructose intolerance. This congenital disorder affects 1 in 21,000 and there have been more than twelve severe complications due to these solutions, most of which were lethal. All the complications occurred in German-speaking countries where fructose and sorbitol are most widely used in parenteral nutrition. Experience over the years has demonstrated that a history of fructose intolerance cannot be obtained, and warning labels on infusion bottles do not avoid this complication. The central European countries are isolated with regard to their use of fructose and sorbitol containing infusion fluids, which involve doubtful advantages but documented lethal risks. Therefore, fructose and sorbitol containing infusion fluids have no further place in our hospital pharmacies.

Fructose↗

Human ketone body production and utilization studied using tracer techniques: regulation by free fatty acids, insulin, catecholamines, and thyroid hormones.

Ketone body concentrations fluctuate markedly during physiological and pathological conditions. Tracer techniques have been developed in recent years to study production, utilization, and the metabolic clearance rate of ketone bodies. This review describes data on the roles of insulin, catecholamines, and thyroid hormones in the regulation of ketone body kinetics. The data indicate that insulin lowers ketone body concentrations by three independent mechanisms: first, it inhibits lipolysis, and thus lowers free fatty acid availability for ketogenesis; second, it restrains ketone body production within the liver; third, it enhances peripheral ketone body utilization. To assess these effects in humans in vivo, experimental models were developed to study insulin effects with controlled concentrations of free fatty acids, insulin, glucagon, and ketone bodies. Presently available data also support an important role of catecholamines in increasing ketone body concentrations. Evidence was presented that norepinephrine increases ketogenesis not only by stimulating lipolysis, and thus releasing free fatty acids, but also by increasing intrahepatic ketogenesis. Thyroid hormone availability was associated with lipolysis and ketogenesis. Ketone body concentrations after an overnight fast were only modestly elevated in hyperthyroidism resulting from increased peripheral ketone body clearance. There was a significant correlation between serum triiodothyronine levels and the ketone body metabolic clearance rate. Thus, ketone body homeostasis in human subjects resulted from the interaction of hormones such as insulin, catecholamines, and thyroid hormones regulating lipolysis, intrahepatic ketogenesis, and peripheral ketone body utilization.

Catecholamines↗

Experimental studies of the application of the Er:YAG laser on dental hard substances: I. Measurement of the ablation rate.

Up to now lasers have not achieved any practical importance in dentistry for drilling teeth because of considerable damage to the surrounding tissue. We studied the application of pulsed 2.94 microns Er:YAG laser radiation in vitro on extracted teeth to remove enamel, dentin, and carious lesions. The depth and diameter of laser-drilled holes were measured as a function of pulse number and radiant exposure. The tissue removal is very effective both for dentin and enamel.

Dental Caries↗

Experimental studies of the application of the Er:YAG laser on dental hard substances: II. Light microscopic and SEM investigations.

Many studies have been undertaken trying to use various laser systems as optical drills on dental enamel and dentin, but the high radiant exposure needed and subsequent high temperature rises lead to fractures of the hard substances and possible damages to the pulp. Compared to the other laser systems, the use of the Er:Yag laser has given encouraging results. Optical and scanning electron microscopy showed only minimal if any damage of the surrounding tissue.

Carbon Dioxide↗

Effects of simvastatin and fenofibrate on serum lipoproteins and apolipoproteins in primary hypercholesterolaemia.

Sixteen patients with primary hypercholesterolaemia received double-blind either fenofibrate (n = 8; 200 mg bid) or the HMG-CoA reductase inhibitor simvastatin (n = 8; 20 mg q.p.m. [corrected] or 40 mg q.p.m. [corrected] if LDL-cholesterol did not fall below 3.6 mmol.l-1 after 4 weeks of treatment). Simvastatin reduced total cholesterol from 9.7 to 7.0 mmol.l-1 after 10 weeks (-28%), and fenofibrate reduced it from 9.2 to 7.7 mmol.l-1 (-15%). The decrease was less during fenofibrate than during simvastatin treatment (time x drug: p = 0.02). Serum LDL-cholesterol fell from 8.3 to 5.3 mmol.l-1 (-36%) during simvastatin and from 7.2 to 6.0 mmol.l-1 (-16%) during fenofibrate administration. Again, the effect of simvastatin was more pronounced than that of fenofibrate (time x drug: p = 0.03). HDL-cholesterol increased significantly from 1.1 to 1.2 mmol.l-1 (+13%) during fenofibrate administration and it did not change significantly during simvastatin. Serum triglycerides fell from 1.3 to 1.1 mmol.l-1 (-16%) during simvastatin, and even more significantly from 2.2 to 1.1 mmol.l-1 (-51%) during fenofibrate (time x drug: p = 0.002). Apolipoprotein B fell on simvastatin from 1.9 to 1.4 g.l-1 (-24%) and from 1.8 to 1.4 g.l-1 (-22%) during fenofibrate. Both drugs were well tolerated and had no significant adverse effects. Simvastatin lowered total and LDL-cholesterol concentrations more than fenofibrate, while the latter had more effect on triglycerides, suggesting specific indications for the two drugs in the treatment of hyperlipoproteinaemias.

Adult↗

Elevation of plasma epinephrine concentrations inhibits proteolysis and leucine oxidation in man via beta-adrenergic mechanisms.

The role of elevated plasma epinephrine concentrations in the regulation of plasma leucine kinetics and the contribution of beta-receptors were assessed in man. Epinephrine (50 ng/kg per min) was infused either alone or combined with propranolol (beta-blockade) into groups of six subjects fasted overnight; leucine flux, oxidation, and net plasma leucine forearm balance were determined during 180 min. Constant plasma insulin and glucagon concentrations were maintained in all studies by infusing somatostatin combined with insulin and glucagon replacements. Plasma leucine concentrations decreased from baseline during epinephrine infusion by 27 +/- 5 mumol/liter (P less than 0.02) due to a 22 +/- 6% decrease in leucine flux (P less than 0.05 vs. controls receiving saline) and to an increase in the metabolic clearance rate of leucine (P less than 0.02). Leucine oxidation decreased by 36 +/- 8% (P less than 0.01 vs. controls). beta-Blockade abolished the effect of epinephrine on leucine flux and oxidation. Net forearm release of leucine increased during epinephrine (P less than 0.01), suggesting increased muscle proteolysis; the fall of total body leucine flux was therefore due to diminished proteolysis in nonmuscle tissues, such as splanchnic organs. Nonoxidative leucine disappearance as a parameter of protein synthesis was not significantly influenced by epinephrine. Plasma glucose and FFA concentrations increased via beta-adrenergic mechanisms (P less than 0.001). The results suggest that elevation of plasma epinephrine concentrations similar to those observed in severe stress results in redistribution of body proteins and exerts a whole body protein-sparing effect; this may counteract catabolic effects of other hormones during severe stress.

Adrenergic beta-Antagonists↗

Contribution of alpha- and beta-receptors to ketogenic and lipolytic effects of norepinephrine in humans.

To assess the effects of alpha- and beta-adrenergic-receptor activation on ketone body kinetics and lipolysis in humans, five groups of overnight-fasted subjects were studied. Group 1 (n = 7) received norepinephrine (NE) to activate alpha- and beta-receptors, resulting in plasma NE concentrations of 1.5 +/- 0.19 ng/ml; group 2 (n = 7) received NE plus beta-blockade; group 3 (n = 7) NE plus alpha-blockade; group 4 (n = 6) NE plus alpha- and beta-blockade; and group 5 (n = 6) saline. Plasma insulin and glucagon concentrations were maintained constant by infusion of somatostatin with insulin and glucagon replacements. Infusion of NE for 170 min resulted in an increase in total ketone body production ([3-14C]acetoacetate infusions) to 8.5 +/- 1.3 vs. 3.9 +/- 0.6 mumol.kg-1.min-1 (P less than .01) in saline controls and in an increase in plasma free fatty acids (FFAs) to 1120 +/- 102 vs. 526 +/- 115 microM (P less than .01) in controls. alpha-Blockade during NE infusion enhanced the lipolytic effect of NE, because plasma FFA increased to 1981 +/- 204 vs. 1301 +/- 146 microM after 45 min (P less than .002), and the ketogenic effect was augmented (14.3 +/- 1.7 vs. 5.6 +/- 0.9 mumol.kg-1.min-1) after 60 min (P less than .001). In contrast, beta-blockade abolished the ketogenic and lipolytic effects of NE to those observed in saline controls. Combined alpha- and beta-blockade during NE infusion was without significant effect on ketone body kinetics and plasma FFA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Ablative effect of an Er:YAG laser on enamel and dentin].

The effectiveness of a pulsed infrared Er:YAG laser beam at a wavelength of 2.94 micron in removing hard tooth structure was studied. The defects produced by the laser beam were evaluated quantitatively and morphologically as a function of energy and pulse frequency. The use of this instrument allows the efficient removal of enamel and dentin while sparing the surrounding tissues.

Dental Cavity Preparation↗

[High frequency sonography in periodontal diagnosis].

In a preparatory series of experimental studies on anatomical preparations of the skull, the components of the bony periodontium have been identified by frontal and horizontal scans. First experimental studies on sheep periodontal have been conducted using a high resolution 20 MHz ultrasound unit. B scans provide a clearly defined image of the periodontal structures of the alveolar arch, the gingiva and the periodontal membrane. Without an additional A scan, however, a quantitative evaluation is impossible.

Alveolar Process↗

[Sonographic TMJ imaging in different sectional planes].

For topographic reasons TMJ arthrosonography is extraordinarily difficult. In a first series of experimental studies on the human skeleton skull the basic principles of ultrasonographic anatomy have been elaborated. To ensure the reproducibility of the results three spatial planes through the TMJ have been defined and--by their characteristic ultrasonographic structures--established as parameters for further studies.

Humans↗

[Evaluation and treatment of obesity in clinical practice].

Obesity continues as before to be a widespread condition. Obesity is defined as a body weight of over 120% of the ideal weight, corresponding roughly to the 85th percentile of the weight distribution. According to the "Build Study" (1979), the ideal weight is assumed to be rather higher than formerly; in men it is 8%, in women 6% less than the so-called normal weight. The latter corresponds roughly to the average weight and is defined as: height (cm) minus 100 in kg. In obese subjects both somatic and psychological complications arise; these are related exponentially to the degree of overweight. More recent findings in the Framingham Study show that obesity leads to coronary heart disease and premature death independently of the classical risk factors. Evaluation of the patient should include a personal and familial history of the obesity, together with individual eating habits and the degree of physical activity indulged in. As assessment should be made of the body fat distribution (android or gynoid obesity); android obesity carries a relatively high risk. Complications should be looked for, together with other risk factors for arteriosclerosis. Treatment depends on the severity of the condition and on the motivation. In general, it should consist of a moderate reduction in the caloric value of the food intake together with advice on eating habits and an increase in bodily activity. Group therapy often gives good results on account of the dynamic interactions within groups. Patients with morbid obesity will profit from a very hypocaloric, "ketogenic" diet (ca. 600-700 kcal/day). One of the author's own studies showed that a very hypocaloric diet resulted in mood elevation and a reduction in the need for sleep. Conservative measures such dietary weight reduction, changes in eating habits and encouragement of bodily activity are to be preferred to surgical treatment (eg, gastric stapling). Weight reductions in hospital do not lead to a change in eating habits and are therefore of doubtful value; drug therapy as a form of long-term treatment is likewise of questionable usefulness.

Adult↗

D-lysergic acid activation and cell-free synthesis of D-lysergyl peptides in enzyme fractions from the ergot fungus Claviceps purpurea.

The D-lysergic acid activating enzyme from the ergot fungus Claviceps purpurea was purified to near homogeneity. It has a native Mr of about 245,000 and in its denatured form is a single polypeptide chain of Mr 62,000. The enzyme catalyzes the ATP-pyrophosphate exchange reaction dependent on D-lysergic acid and, though much less, that dependent on dihydrolysergic acid. Western blot analysis of SDS electropherograms of crude protein extracts from C. purpurea using monospecific antibodies directed against the D-lysergic acid activating enzyme revealed the immunostaining of one particular band which was identical with that of the D-lysergic acid activating enzyme. No significant immunoreactive band with higher molecular weight was seen, which precludes the possibility that the enzyme had arisen from the proteolysis of a high molecular weight ergot peptide synthetase. An ammonium sulfate fractionated enzyme fraction was prepared from C. purpurea strain C1 that catalyzed the incorporation of D-lysergic acid into two peptides which besides D-lysergic acid contained alanine, phenylalanine, and proline. Dihydrolysergic acid was efficiently incorporated into the corresponding dihydrolysergic acid containing analogues of the two compounds. Radiochemical analysis and degradation studies suggest that the two D-lysergic acid containing peptides most probably are N-[N-(D-lysergyl)-L-alanlyl]-L-phenylalanyl-L-proline lactam and N-[N-(D-lysergyl)-L-analyl]-L-phenylalanyl-D-proline lactam, respectively. N-[N-(D-Lysergyl)-L-alanyl]-L-phenylalanyl-L-proline lactam is considered to be the immediate precursor of ergotamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell-Free System↗

Interaction of cortisol and epinephrine in the regulation of leucine kinetics in man.

To assess the interaction of the two major stress hormones epinephrine and cortisol in the regulation of leucine kinetics in man, epinephrine (50 ng/kg/min) was infused either alone or in combination with cortisol (2 micrograms/kg/min) into two groups of 6 postabsorptive normal male subjects during 180 min. Plasma leucine concentrations decreased by 28% (p less than 0.05) from baseline during epinephrine treatment (plasma levels 515 pg/ml); this was due to a decrease of leucine appearance (determined by 1-13C-leucine infusions) by 23% (p less than 0.025); leucine oxidation decreased by 29% (p less than 0.05). However, when plasma cortisol concentrations were elevated to supraphysiological levels (16.3 mumol/l) during epinephrine administration, the decreases of leucine plasma concentrations, appearance and oxidation were abolished. Plasma glucose and FFA concentrations were similarly elevated during both kinds of treatment. Since leucine appearance represents a measurement of total body protein breakdown and leucine disappearance into non-oxidative pathways reflects protein synthesis, the data indicate that plasma epinephrine concentrations during severe stress exert a protein anabolic effect in man which may counteract catabolic properties of elevated plasma cortisol.

Adult↗

Effect of insulin on ketone body clearance studied by a ketone body "clamp" technique in normal man.

The effect of elevated plasma insulin concentration (55 +/- 2 mU/l) on peripheral clearance and production of total ketone bodies was determined using 3-14C-acetoacetate tracer infusions. Nine normal subjects were studied twice, once during insulin infusion (20 mU.m-2.min-1), once during basal plasma insulin concentrations (controls). Blood total ketone body concentrations (sum of acetone, acetoacetate and beta-hydroxybutyrate) were maintained in both studies at 2 mmol/l by feedback-controlled sodium acetoacetate infusions. The coefficient of variation of total ketone body concentrations during the two clamp studies was 10 and 11% respectively. The sodium acetoacetate infusion rate required during the clamp was 55 +/- 4% higher during hyperinsulinaemia than in controls (p less than 0.005). This was due to increased total ketone body clearance (8.4 +/- 0.7 vs 6.7 +/- 0.4 ml.kg-1.min-1, p less than 0.015), and to enhanced suppression of ketone body production (p less than 0.01). Hyperketonaemia alone decreased ketone body production by 42% and diminished ketone body clearance by 46%, the former being enhanced, the latter being in part antagonised by insulin. Since the plasma insulin concentrations were within those observed in patients treated for diabetic ketoacidosis, the data suggest that the antiketotic effect of insulin therapy results in part from an increase in peripheral ketone body disposal.

Acetoacetates↗